Mycology

Aspergillosis – Causative Agent, Symptoms, Types, Treatment

Aspergillus species are responsible for a wide variety of diseases in humans, ranging from direct invasion to hypersensitivity reactions. The majority of...

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This article writter by MN Editors on November 09, 2022

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Aspergillosis - Causative Agent, Symptoms, Types, Treatment
Aspergillosis - Causative Agent, Symptoms, Types, Treatment | Image Source: https://resident360.nejm.org/content-items/aspergillosis

Aspergillus species are responsible for a wide variety of diseases in humans, ranging from direct invasion to hypersensitivity reactions. The majority of human diseases are caused by Aspergillus fumigatus and Aspergillus niger, and less frequently by Aspergillus flavus and Aspergillus clavatus.

Aspergillus, the mould (a type of fungus) that causes aspergillosis, is prevalent both inside and outdoors; hence, the vast majority of individuals inhale fungal spores daily. It is virtually difficult to prevent breathing in Aspergillus spores entirely. For individuals with sound immune systems, inhaling Aspergillus is harmless. Breathing in Aspergillus spores can induce an infection in the lungs or sinuses that can spread to other parts of the body in those with compromised immune systems.

Properties of Aspergillus Species 

  • The species of Aspergillus are moulds.
  • They feature septate hyphae that generate dichotomous branches in the shape of a V. The Aspergillus species are distinguished by (a) their physical characteristics, (b) the development pattern of their conidiophores, and (c) the colour of their conidia.
  • Hyphae of the Aspergillus species are characterised by the presence of septate hyphae that branch at 45° angles. Silver stains are the most effective at revealing hyphae in tissues. In contrast to Mucor and Rhizopus, where the hyphae walls are more or less uneven, the hyphae walls are roughly parallel.
  • The treatment of the colonies with Lactophenol cotton blue (LPCB) reveals septate hyphae and branching conidiophores. Conidia organised in chains are seen on elongated cells called sterigmata. The latter is present on the conidiophores’ vesicle. Aspergillus conidia often form radiating chains, in contrast to those of Rhizopus and Mucor, which are contained within sporangia.
  • At 25 degrees Celsius, the fungus grows fast on SDA and other culture medium. Aspergillus develops colonies within one to two days and has a velvety exterior.

Types of aspergillosis

  • Allergic bronchopulmonary aspergillosis (ABPA): Occurs when Aspergillus produces lung inflammation and allergy symptoms such coughing and wheezing, but does not cause an infection.
  • Allergic Aspergillus sinusitis: Occurs when Aspergillus induces inflammation in the sinuses and sinus infection symptoms (drainage, stuffiness, headache) but does not cause an infection.
  • Azole-Resistant Aspergillus fumigatus: Occurs when one species of Aspergillus, A. fumigatus, develops resistance to specific treatments. Patients with resistant infections may not respond to therapy.
  • Aspergilloma: Aspergilloma occurs when a ball of Aspergillus forms in the lungs or sinuses, but does not typically spread to other areas of the body. 4 Aspergilloma is also known by the term “fungus ball.”
  • Chronic pulmonary aspergillosis: Occurs when an Aspergillus infection creates cavities in the lungs, and is a potentially long-lasting (three months or longer) illness. Additionally, one or more aspergillomas may be present in the lungs.
  • Invasive aspergillosis: Occurs when Aspergillus creates a severe infection; typically affects individuals with compromised immune systems, such as those who have undergone an organ transplant or stem cell transplant. Aspergillosis invasive often affects the lungs, but it can also extend to other organs.
  • Cutaneous (skin) aspergillosis: Occurs when Aspergillus enters the body through a break in the skin (e.g., after surgery or a burn) and causes infection, typically in immunocompromised individuals. Cutaneous aspergillosis can also develop if invasive aspergillosis spreads to the skin from another organ, such as the lungs.

Pathogenesis and Immunity 

  • Immunocompetent humans are seldom infected by Aspergillus species. They primarily cause invasive infections in immunocompromised patients due to (a) immunosuppressive drug use, (b) underlying lung disease, or (c) immunodeficiency illnesses such as HIV.
  • In immunocompromised hosts, Aspergillus species cause blood invasion, resulting in lung tissue infarction, bleeding, and necrosis.
  • Additionally, Aspergillus spp. creates toxic compounds that block macrophage and neutrophil phagocytosis, hence aiding the infection’s spread.
  • Aspergillus species, unlike Candida species, are not part of the natural human flora. They are widespread in the environment; hence, most infection transmission is external.

Clinical Syndromes 

Aspergillus species may largely damage the lungs in immunocompetent hosts, resulting in four major syndromes: (a) allergic bronchopulmonary aspergillosis, (b) chronic necrotizing aspergillus pneumonia, (c) aspergilloma, and (d) invasive aspergillosis.

  • Allergic bronchopulmonary aspergillosis: Allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to tracheobronchial tree-colonized A. fumigatus organisms. This disease frequently occurs alongside asthma and cystic fibrosis.
  • Chronic necrotizing pulmonary aspergillosis: Chronic necrotizing pulmonary aspergillosis is a subacute illness that affects immunocompromised patients. In conjunction with drinking, underlying pulmonary disease, or continuous corticosteroid medication, the syndrome manifests.
  • Aspergilloma: Aspergilloma is a disease that develops in a preexisting lung parenchymal cavity. This cavity may have been produced by tuberculosis, sarcoidosis, cystic fibrosis, or emphysematous bullae at a previous time. The condition is marked by the presence of a fungal ball inside the cavity. However, the fungus does not infiltrate the cavity. It could result in hemoptysis.
  • Invasive aspergillosis: Aspergillosis invasive is an infection that progresses fast in immunocompromised persons. The disease is generally lethal. In immunocompromised hosts, Aspergillus species create a widespread disease that manifests as endophthalmitis, endocarditis, and abscesses in the viscera, including the liver, spleen, kidney, and soft tissues and bone.

Epidemiology 

  • Globally, diverse clinical symptoms of Aspergillus infection have been recorded.
  • The incidence of allergic bronchopulmonary aspergillosis in patients with asthma in the United Kingdom has been observed to increase.
  • Aspergillus species, unlike Candida species, are not part of the natural human flora.
  • They are widespread in the environment; hence, most infection transmission is external.

Laboratory Diagnosis 

  • The laboratory diagnosis of invasive aspergillosis or chronic necrotizing aspergillus pneumonia hinges on the direct microscopy and culture of Aspergillus in tissue.
  • The specimen’s direct KOH preparation reveals nonpigmented, septate hyphae with distinctive dichotomous branching at a 45° angle. Tissue biopsies reveal septate, branching hyphae penetrating the tissues.
  • The specimens are inoculated on SDA without cycloheximide and incubated for one to two days at 25 degrees Celsius. Different kinds of Aspergillus create colonies of varying hues. A. fumigatus forms grey colonies, while A. niger and A. flavus form black and yellowish-green colonies, respectively. Culture-based isolation of Aspergillus must be viewed with caution due to their prevalence as laboratory contamination. The repeated isolation of fungus may be useful in determining the harmful role of Aspergillus.
  • Serum galactomannan estimation is beneficial for diagnosing invasive aspergillosis. The presence of increased galactomannan in bronchoalveolar lavage can also be utilised to diagnose pulmonary aspergillosis.
  • A positive skin test for Aspergillus fumigatus confirms the presence of allergic bronchopulmonary aspergillosis. Positive serology for Aspergillus precipitation or Aspergillus-specific IgG or IgE antibodies are suggestive of the disorder, as is a serum IgE level of 1000 IU/ml.
  • In cases of aspergilloma, serum IgG levels are typically elevated.

Treatment 

  • Most typically, amphotericin B is used to treat invasive aspergillosis. However, therapy results are not satisfactory.
  • Caspofungin is a substitute for amphotericin B for patients who do not respond to it. Best treatment for aspergilloma is surgical excision of the fungus ball from the cavity.

Prevention and Control 

It is impossible to prevent breathing in Aspergillus spores due to the prevalence of the fungus in the environment. There may be techniques to reduce the likelihood that immunocompromised individuals will get a severe Aspergillus infection.

  • Protect yourself from the environment: Not only are these actions suggested, but they have not been proved to prevent aspergillosis. Avoid dusty environments such as construction and excavation sites. Wear a N95 respirator (a form of face mask) if you cannot avoid these regions. Click here for additional details on respirators. Avoid activities involving close contact with soil or dust, such as gardening and yard maintenance. Unless this is feasible, Wear shoes, long pants, and a long-sleeved shirt when engaging in outside activities like gardening, yard labour, or forest exploration. When handling things such as soil, moss, or manure, use gloves. To lessen the likelihood of getting a skin infection, thoroughly cleanse skin wounds with soap and water, particularly if they have been exposed to soil or dust.
  • Antifungal medication: Your healthcare practitioner may give aspergillosis prevention medication if you are at high risk for developing invasive aspergillosis (e.g., if you’ve had an organ transplant or a stem cell transplant). Scientists are still discovering which transplant patients are at the most risk for fungal infections and how to best prevent them.
  • Predicting the onset of infection: Blood testing to detect invasive aspergillosis may be beneficial for certain high-risk patients. Consult with your physician to determine if this sort of test is appropriate for you.

Who gets aspergillosis?

Different kinds of aspergillosis afflict distinct populations.

  • The majority of patients with allergic bronchopulmonary aspergillosis (ABPA) have cystic fibrosis or asthma.
  • Aspergillomas typically affect individuals with other lung disorders, such as tuberculosis. Also known as a “fungus ball”
  • People with lung disorders such as tuberculosis, chronic obstructive pulmonary disease (COPD), or sarcoidosis commonly develop chronic pulmonary aspergillosis.
  • Invasive aspergillosis affects individuals with compromised immune systems, such as those who have received a stem cell or organ transplant, are undergoing chemotherapy for cancer, or are taking high amounts of corticosteroids. There have been reports of invasive aspergillosis among hospitalised individuals with severe influenza.

References

  • https://www.mayoclinic.org/diseases-conditions/aspergillosis/symptoms-causes/syc-20369619#:~:text=Aspergillosis%20is%20an%20infection%20caused,is%20everywhere%20%E2%80%94%20indoors%20and%20outdoors.
  • https://www.cdc.gov/fungal/diseases/aspergillosis/index.html
  • https://my.clevelandclinic.org/health/diseases/14770-aspergillosis
  • https://en.wikipedia.org/wiki/Aspergillosis
  • https://www.ncbi.nlm.nih.gov/books/NBK482241/
  • https://rarediseases.org/rare-diseases/aspergillosis/
  • https://www.healthline.com/health/aspergillosis
  • https://medlineplus.gov/ency/article/001326.htm
  • https://emedicine.medscape.com/article/296052-overview
  • https://www.cdc.gov/fungal/diseases/aspergillosis/symptoms.html
  • https://err.ersjournals.com/content/20/121/156
  • https://www.nhs.uk/conditions/aspergillosis/
  • https://medlineplus.gov/aspergillosis.html
  • https://www.thoracic.org/patients/patient-resources/resources/aspergillosis.pdf
  • https://thorax.bmj.com/content/70/3/270
  • https://www.msdmanuals.com/en-in/professional/infectious-diseases/fungi/aspergillosis
  • https://www.uptodate.com/contents/diagnosis-of-invasive-aspergillosis
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